Vaccination against pathogens has been one of the major accomplishments of medicine over the past century. While effective vaccines have been developed for a large number of diseases, development of safe and effective vaccines for a number of other diseases remains problematic. For example, the most commonly used approach for inactivation of enveloped viruses is cross-linking of surface glycoproteins by formaldehyde. While this approach results in inactivation of the enveloped viruses, covalent cross-linking of the surface proteins can severely distort the structure of immunogenic epitopes (Koch et al., Apmis 104:115-25 (1996)). The use of inactivated or killed microbial agents as a vaccine, although generally safe, will not always be effective if the immunogenic characteristics of the agent are altered. Indeed, the preferential degradation of certain antigens on the inactivated microorganisms might produce a weak or poorly targeted immune response that permits a pathological response when the host is later challenged with the live microorganism. On the other hand, while the preparation of live attenuated microbial agents as vaccines will often provide improved immunologic reactivity, use of such live attenuated microbial agents has an increased risk that the vaccine itself will be infectious. Such live attenuated vaccines can be infectious, for example, as a result of reversion, or the organism may be able to propagate and provide a reservoir for future infection.
Thus, one must generally choose between improved effectiveness and greater degree of safety when selecting between the viral inactivation and viral attenuation techniques for vaccine preparation. The choice is particularly difficult when the virus is resistant to inactivation and requires highly rigorous inactivation conditions that are likely to degrade the antigenic characteristics.
It is therefore desirable to provide improved methods for inactivating agents such as viruses, bacteria, cancer cells and other cell types, where the methods are capable of inactivating these agents without causing substantial degradation of the antigenic structure of the agents. In particular, the inactivated agents should be useful as vaccines and free from adverse side effects at the time of administration as well as upon subsequent challenge with the live agent.